Décryptage
Text: Geneviève Ruiz
Photo: Zephyr / Science Photo Library

Coma: predicting wake-up

Doctors are managing to predict with ever more accuracy whether or not a comatose patient will wake up one day. We explore a world that is still rife with the unknown.

Mar 16, 2014

Follow Up

A patent was filed, via the Technology Transfer Office (PACTT), for the discovery made by the University of Lausanne (UNIL) and Lausanne University Hospital (CHUV) teams on predicting the probability that a comatose patient will wake up. Marzia De Lucia and Athina Tzovara were the inventors. “We wanted to develop software that automatically integrates the measurements and calculations,” says project coordinator Marzia De Lucia of the Centre for Biomedical Imaging at the CHUV. “We are already in contact with several potential partners in order to think about how to develop an instrument that could incorporate this programme.”

Will a patient wake up one day from a coma? Answering this question is a considerable challenge for doctors, given the complexity of this brain dysfunction. Through extensive research and increasingly precise equipment, the coma is gradually being demystified. “Since 2010, we have performed a battery of tests using a sophisticated EEG, which allows us to develop a detailed map of the brain,” explains Mauro Oddo, head of the Neurointensive Care Unit at the Lausanne University Hospital (CHUV). “We subject patients to a series of sensory stimuli and observe their reactions. On that basis, it is possible to predict whether a patient will remain comatose with a probability of over 80%, particularly in a post-cardiac arrest coma.”

This probability could improve significantly following recent advances in research. In France, at the Pitié-Salpêtrière Hospital in Paris, a team created a bank containing the data of hundreds of seriously injured people seriously whose prognosis at one year was known. When a new patient arrives in the intensive care unit, the results of his MRI scan are compared with those of the bank using special software. So far, predictions thus obtained, pertaining to the likelihood of patients waking up or the after-effects they may suffer, have proved to be reliable.

However, the real revolution could come from a recent study at the Centre for Biomedical Imaging (CIBM) in Lausanne, the joint work of Mauro Oddo and Andrea Rossetti, head doctor of the Epileptology Unit at the CHUV. The results, published in the “Brain journal”, have exceeded expectations: “For now, we have obtained predictions that were 100% accurate,” says a delighted Mauro Oddo. “Since 100% obviously does not exist in medicine, we need to confirm these results with a larger group of
patients,” he specifies.

The test consists of subjecting patients to different auditory stimuli, then observing the reaction of their brains with an EEG. “In the intensive care phase, we place the patient in a state of hypothermia for 12 hours and we lower body temperature to 33 degrees,” explains Mauro Oddo. “This treatment helps preserve brain function. This is when we begin to look at the person’s brain, observing his reaction to
a series of monotone sounds that vary in intensity and duration.” Twenty-four hours later, when the patient has been warmed up and returned to a normal temperature, the medical team repeats the test. If it observes an improvement between the first and second session, the comatose patients have so far always woken up.

BETWEEN MYTH AND REALITY

A patient is in a coma for four years and becomes pregnant. She wakes up after giving birth to a stillborn child and then goes on to lead a completely normal life. Alicia, the heroine of the film Talk to Her (Hable con ella) by Spanish director Pedro Almodovar, would certainly not know the same fate in real life. “Most patients do not remain in a coma for more than four to six weeks,” explains Mauro Oddo, head of the Neurointensive Care Unit at the CHUV. “And it seems very unlikely that a woman in a coma could fall pregnant, given that her hormonal cycles are disrupted.”

Beyond fiction, beliefs about comas are also influenced by exceptional cases reported in the media, such as the American Terry Wallis, who in 2003 said the name of his mother after 20 years in a coma.

Moreover, the term “coma” is often used carelessly. There are actually different stages of brain dysfunction, characterised by clear signs. “Between coma and waking, the patient often goes through a vegetative state, then enters a minimally conscious state,” clarifies Andrea Rossetti, head doctor of the Epileptology Unit at the CHUV.” In the latter state, patients are more responsive to external stimuli. For example, they are able to smile or to follow their own reflection in a mirror. Even if they cannot communicate with those around them continuously, there is still a likelihood that they may come out of their state one day. The more weeks go by, however, the slimmer the chances...”

Between fiction and exception

CONVENTIONAL The former Israeli Prime Minster, Ariel Sharon, has been in a vegetative state for seven years.

UNUSUAL The American Terry Wallis said the name of his mother after 20 years spent in a coma.

IMPROBABLE Alicia, the heroine of the film «Talk to Her», becomes pregnant during her coma.

Major ethical issues

“To date, we have tested only 30 patients, which is not enough,” says Mauro Oddo. “We are in the process of testing others, but we would like to test hundreds to confirm our results.” This promising experiment has only been conducted on people for whom the cause of coma is prolonged cardiac arrest. The researchers would also like to apply it to brain injury victims. “We are beginning to study this section of the population, since the people involved are often younger than 40 years old. This is especially true since, even if the chances of waking up are practically nil, it is still very painful to disconnect a young person in a coma.”

The results of these tests will facilitate decision-making that is often very distressing for families and medical staff. When faced with comatose patients, ethical questions frequently arise. “In Switzerland, when we know that a patient is not going to wake up, we do not keep him on life support,” says Andrea Rossetti. “A case like Ariel Sharon, the former Israeli Prime Minster, who has been in a vegetative state for seven years following a stroke, could not exist here. These questions are highly cultural and in countries such as Italy, Japan and Israel, it is very difficult to stop treatment for a person, even if there is no hope.”

There are tragic situations, such as the one concerning Terri Schiavo, whose fate divided America in 2005. This 41-year-old woman was in a vegetative state for 15 years following a stroke. Her husband was resigned to ending her suffering. Her parents did not agree, and a series of conflicting court rulings ensued. On two occasions, Terri Schiavo’s artificial feeding tube was removed, then reinstalled, first in 2001, then in 2003, and permanently disconnected two years later.⁄



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COMA

A patient in a coma cannot be awakened by any stimulation, even involving pain. His eyes remain closed and he has no sleep-wake cycle. The only movements he makes are reflex ones.

VEGETATIVE STATE

This state is characterised by the preservation of certain functions: breathing, thermoregulation and sleep-wake cycles. The patient may spontaneously open his eyes, but does not communicate with the outside world and does not respond to stimuli. His movements are reflexes.

MINIMALLY CONSCIOUS STATE (MCS)

The patient shows some awareness of his environment: he looks at an object, follows his reflection in a mirror, sometimes reacts to emotional stimuli (he may cry or smile when he sees a loved one) and can answer requests, for example, by moving. But this behaviour is fleeting and unstable. The patient is unable to communicate consistently.

This coloured tomogram represents the brain of a 42-year-old coma patient. The lesions, in particular on the mesencephalon (white marks), a region controlling functions such as concentration, sleep, waking up, and movements of the head and neck, are caused by a lack of oxygen.